mycophenolic-acid and Myositis

To review advances in the management of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-associated ILD) in the past 5 years, with highlights in myositis-specific antibody (MSA) groups.. With the recent advent of widespread MSA testing, the study of specific homogeneous autoantibody-based subgroups of IIM-associated ILD is now possible. The prevalence, severity, prognosis, and response to treatment are under study for these individual MSAs. Early evidence suggests that PL-7- and PL-12-positive patients are more likely to have ILD and worse severity, compared to Jo-1 patients. Many medications have been efficacious for the treatment of IIM-associated ILD, including calcineurin inhibitors, rituximab, and cyclophosphamide. We suggest vigilant screening and monitoring of ILD in IIM patients with focus on the potential side effects associated with therapy and thus advocate appropriate vaccination, PCP prophylaxis, and bone health protection. Many different agents are used to manage patients with ILD with no comparative effectiveness studies to guide the clinician. The possibility of using MSAs to help guide treatment decisions is an appealing, although unproven, focus of research. Unfortunately, the rarity of non-Jo-1 myositis-specific antibodies has precluded robust study of response to treatment and overall management. Ongoing clinical trials and working groups are coordinating efforts to provide evidence-based management.

Topics: Autoantibodies; Autoimmune Diseases; Azathioprine; Calcineurin Inhibitors; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Mycophenolic Acid; Myositis; Rituximab

The management of patients with idiopathic inflammatory myopathy (IIM) remains a challenge given the systemic features beyond active myositis. That is, recognizing the inflammatory arthropathy, varying dermatomyositis rashes, and overt and occult features of interstitial lung disease in addition to myositis adds to the complexity of diagnosis and treatment of IIM. However, clinicians now have available many more immunosuppressive drugs as well as biologic agents for use in patients with myositis and other autoimmune diseases. Here, the use of these agents is reviewed and support based on available published literature is provided even though many studies have been small and results somewhat anecdotal. Glucocorticoids remain the initial treatment of choice in most instances and methotrexate and azathioprine are often used early in the treatment course. These agents are followed by other immunosuppressive drugs, for example mycophenolate mofetil, tacrolimus, cyclosporine and cyclophosphamide, some of which are used alone while combinations of these agents also provide an effective option. There is more rationale for the use of biologic agents such as rituximab from a mechanistic perspective and, given the incorporation of validated core set measures in assessing myositis patients, we can look forward to better designed clinical trials in the future.

Topics: Adrenocorticotropic Hormone; Adult; Azathioprine; Cyclophosphamide; Cyclosporine; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Myositis; Tacrolimus

Treatment of organ involvements accompanied by systemic autoimmune diseases is still challenging for clinicians, reminding the existence of unmet needs. Among them, lupus nephritis (LN), neuropsychiatric lupus, interstitial lung diseases (ILD) complicated with polymyositis/dermatomyositis (PM/DM) or systemic sclerosis (SSc) are the most severe conditions with poor prognosis. Because of the rarity and severity of the disease status, and of variety in evaluation methods, randomized clinical trials tend to be difficult in recruiting patients, in designing protocols, and in meeting primary endpoints. In such tough conditions, superiority of IVCY over corticosteroids alone for LN has been established, which is now going to be replaced by mycophenolate mofetil (MMF). Moreover, non-inferiority of tacrolimus to MMF is reported and efficacy of biologics such as Rituximab and Abatacept for LN is under investigation. In contrast, PM/DM-ILD is not suitable for randomized controlled trial because of the severity/acute progression in some patients. Intensive immunosuppressive regimen is recommended for those with poor prognostic factor(s). Cyclophosphamide has limited efficacy in SSc-ILD. Hematopoietic stem cell transplantation elongated patient survival and improved ILD, but with high treatment-related mortality rate. Efficacy of rituximab and MMF has been reported in small-sized trials. In this review, previously established treatment as well as emerging immunotherapies for organ involvements will be discussed. Our experiences in autoimmune settings also will be introduced.

Topics: Administration, Oral; Autoimmune Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Immunotherapy; Lupus Erythematosus, Systemic; Mycophenolic Acid; Myositis; Prognosis; Rituximab; Scleroderma, Systemic

Mycophenolate mofetil (MMF) is an inhibitor of inosine monophosphate dehydrogenase, which affects de novo purine synthesis and T- and B-cell proliferation. So far its efficacy and safety as an immunosuppressive treatment have been proven in organ transplantations and also in various autoimmune diseases. A literature search was conducted by using PubMed and the Cochrane library. This review focuses primarily on current treatment with MMF for systemic lupus erythematosus, systemic sclerosis, vasculitis and idiopathic inflammatory myopathies.

Topics: Connective Tissue Diseases; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Myositis; Scleroderma, Systemic; Vasculitis

Inflammatory muscle disease is a term used to designate a heterogeneous group of autoimmune diseases of unknown etiology whose main target is the skeletal muscle. Clinical, histological, and immunopathological criteria are classically used to distinguish polymyositis, dermatomyositis, and inclusion body myositis. Major obstacles to controlled therapeutic trials in patients with inflammatory muscle diseases include the heterogeneity of these diseases, their low prevalence, and the absence of validated evaluation criteria. To date, no such trials are available and the treatment is therefore largely empirical. Glucocorticoids are usually given first. Methotrexate is then added in the event of resistance to, or dependency on, glucocorticoid therapy. Methotrexate may be used from the outset in patients with severe disease in an attempt to decrease the glucocorticoid requirements. However, no controlled trials have been conducted to determine whether first-line methotrexate therapy improves outcomes. Intravenous immunoglobulin infusion is a costly treatment option that is reserved for the following situations: refractory dermatomyositis, based on a trial showing superiority over a placebo; myositis with impaired swallowing; and patients with contraindications to immunosuppressants. In patients who fail second-line treatment, which usually consists of methotrexate plus a glucocorticoid, the diagnosis should be carefully reappraised before other treatment options are considered. These options include methotrexate plus azathioprine and recently introduced drugs such as mycophenolate mofetil and rituximab. Caution is in order when considering TNFα antagonist therapy, as cases of paradoxical exacerbation of the muscle involvement have been reported.

Topics: Antibodies, Monoclonal, Murine-Derived; Disease Progression; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Lung Diseases, Interstitial; Mycophenolic Acid; Myositis; Receptors, Interleukin-1; Remission Induction; Rituximab; Tumor Necrosis Factor-alpha

The objective of this study was to evaluate the efficacy and safety of MMF in juvenile idiopathic inflammatory myopathies (JIIMs).. Patients diagnosed with JIIM and treated with MMF enrolled in the Juvenile Dermatomyositis Research Group (JDRG) in the UK or followed at the Giannina Gaslini Institute in Genoa, Italy, were included. The following information was collected retrospectively at MMF initiation, at 3, 6 and 12 months after treatment start, and at last follow-up visit: clinical manifestations, laboratory data, physicians' subjective assessment of disease activity, standardized outcome measures of muscle strength/endurance, cutaneous disease activity, physical function, global disease activity, cumulative damage, and ongoing treatment.. Of the 29 patients included, 23 had juvenile DM and 6 had overlap myositis. During administration of MMF, improvement in measures of muscle strength, skin disease activity, and overall disease activity was seen, with an increase in the frequency of normal scores for Manual Muscle Test-8 from 50.0% to 83.3%, Childhood Myositis Activity Score from 53.5% to 88.9%, muscle component of DAS from 55.2% to 84.2%, skin component of DAS from 31.0% to 42.1%, visual analogue scale for skin disease activity from 25.0% to 47.4%, and visual analogue scale for overall disease activity from 7.1% to 42.1%. The number of patients with inactive disease increased from 10.3% at baseline to 68.5% at last follow-up. CS dose was significantly reduced, from 0.3 to 0.1 mg/kg/day. No relevant side effects were reported.. Our experience suggests that MMF is a valuable therapeutic option for the management of JIIM.

Topics: Child; Dermatomyositis; Humans; Mycophenolic Acid; Myositis; Retrospective Studies; Skin

Autoimmune disorders can affect various organs and if refractory, can be life threatening. Recently, CD19-targeting-chimeric antigen receptor (CAR) T cells were efficacious as an immune suppressive agent in 6 patients with refractory systemic lupus erythematosus and in 1 patient with antisynthetase syndrome.. To test the safety and efficacy of CD19-targeting CAR T cells in a patient with severe antisynthetase syndrome, a complex autoimmune disorder with evidence for B- and T-cell involvement.. This case report describes a patient with antisynthetase syndrome with progressive myositis and interstitial lung disease refractory to available therapies (including rituximab and azathioprine), who was treated with CD19-targeting CAR T cells in June 2022 at University Hospital Tübingen in Tübingen, Germany, with the last follow-up in February 2023. Mycophenolate mofetil was added to the treatment to cotarget CD8+ T cells, hypothesized to contribute to disease activity.. Prior to treatment with CD19-targeting CAR T cells, the patient received conditioning therapy with fludarabine (25 mg/m2 [5 days before until 3 days before]) and cyclophosphamide (1000 mg/m2 [3 days before]) followed by infusion of CAR T cells (1.23×106/kg [manufactured by transduction of autologous T cells with a CD19 lentiviral vector and amplification in the CliniMACS Prodigy system]) and mycophenolate mofetil (2 g/d) 35 days after CD19-targeting CAR T-cell infusion.. The patient's response to therapy was followed by magnetic resonance imaging of the thigh muscle, Physician Global Assessment, functional muscle and pulmonary tests, and peripheral blood quantification of anti-Jo-1 antibody levels, lymphocyte subsets, immunoglobulins, and serological muscle enzymes.. Rapid clinical improvement was observed after CD19-targeting CAR T-cell infusion. Eight months after treatment, the patient's scores on the Physician Global Assessment and muscle and pulmonary function tests improved, and there were no detectable signs of myositis on magnetic resonance imaging. Serological muscle enzymes (alanine aminotransferase, aspartate aminotransferase, creatinine kinase, and lactate dehydrogenase), CD8+ T-cell subsets, and inflammatory cytokine secretion in the peripheral blood mononuclear cells (interferon gamma, interleukin 1 [IL-1], IL-6, and IL-13) were all normalized. Further, there was a reduction in anti-Jo-1 antibody levels and a partial recovery of IgA (to 67% of normal value), IgG (to 87%), and IgM (to 58%).. CD19-targeting CAR T cells directed against B cells and plasmablasts deeply reset B-cell immunity. Together with mycophenolate mofetil, CD19-targeting CAR T cells may break pathologic B-cell, as well as T-cell responses, inducing remission in refractory antisynthetase syndrome.

Topics: Antigens, CD19; Cyclophosphamide; Humans; Immunosuppressive Agents; Immunotherapy, Adoptive; Leukocytes, Mononuclear; Lung Diseases, Interstitial; Mycophenolic Acid; Myositis; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen

Idiopathic inflammatory myopathies (IIMs) form a heterogeneous group of disorders with a deficit of quality evidence regarding its management. Therefore, we aimed to explore the prevalent treatment practices in the MyoCite cohort from India.. Drug usage patterns, their predictors, drug retention rates, efficacy, and adverse drug reactions were analyzed for adults and children newly diagnosed with IIM (2017-2020) and followed prospectively and compared with real-world data by performing a medical records review. GraphPad Prism version 8.4.2 was used for statistical analysis.. Of 181 adults (male-to-female ratio, 1:4.6) and 30 children (M:F, 1.3:1), dermatomyositis (41% adults, 93% children) was the most common subtype. Methotrexate (MTX) was the drug of choice (67% adult, 90% children) followed by azathioprine (AZA) and mycophenolate mofetil (MMF). The MMF, AZA, cyclophosphamide, and rituximab (RTX) were preferred for those with antisynthetase syndrome (ASSD) and those with lung involvement, whereas MTX was avoided in them. Functional class and family income did not determine drug preferences. Glucocorticoids were initiated at a lower dose in overlap myositis (45% vs 80%, p = 0.001), and the time to achieve the lowest dose of glucocorticoids was longer than 24 months for ASSD (77% vs 14%, p = 0.002).Over a median of 35 months, the overall retention rate was the highest for RTX (75%) followed by MTX (58%). Relapse-free survival was the highest for RTX followed by MTX. The most common reasons for discontinuation were adverse drug reactions for MTX and MMF, inefficacy for AZA, and cost for RTX.. In this first analysis of drug usage and retention in patients with IIM in Northern India, MTX emerged as the most preferred drug in both adults and children, with the exception of those with ASSD or lung disease. Organ involvement and subtype of IIM are key determinants of drug preference. Overall, RTX and MTX were well-tolerated with high retention rates, followed by AZA and MMF.

Topics: Adult; Azathioprine; Child; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Myositis; Pharmaceutical Preparations; Registries; Treatment Outcome

The peculiar presentation of overlap syndrome in children makes precise diagnosis difficult. Children with overlap syndrome may or may not have specific antibodies. We present the case of a 12-year-old girl diagnosed with overlap syndrome of systemic lupus erythematosus (SLE) and juvenile polymyositis (JPM) who tested positive for anti-OJ antibodies.. We describe the case of a 12-year-old girl diagnosed with SLE at the age of 7 and presented with fever with malar rash, periungual erythema, generalized weakness, and multiple joint pain at admission. The patient had persistent joint pain and weakness after intravenous methylprednisolone administration and complained of an inability to walk with a positive test for Gower's sign one week after admission, accompanied by elevated alanine aminotransferase (ALT) and creatine-phospho-kinase (CPK) levels. The results of nerve conduction velocity test were normal. Electromyography revealed abundant spontaneous activity and myopathic motor unit action potentials in the right deltoid, biceps, and iliopsoas, in addition to fibrillation and mild myopathic motor unit action potentials in the right rectus femoris muscle. Magnetic resonance imaging revealed diffusely increased signal intensities in the myofascial planes of the bilateral iliopsoas, gluteus, obturator, pectineus, and hamstring muscles. Anti-nuclear antibody, anti-RNP, and rheumatoid factor IgG tests were positive, and inflammatory myopathy autoantibodies revealed anti-OJ antibody positivity, which strongly indicated autoimmune myositis. High-resolution computed tomography of the lung revealed mild pericardial effusion without any evidence of interstitial lung disease. We initiated intravenous pulses of methylprednisolone treatment, followed by cyclosporine, mycophenolate mofetil, and oral steroids. Clinical improvement with a delayed, slowly reduced CPK level after the above treatment and she was discharged after the 18th day of hospitalization.. Overlap syndrome with inflammatory myositis can occur years later in pediatric SLE cases. We should be alert when patients with SLE develop a new presentation characterized by decreased SLE-specific autoantibody titers, positive anti-RNP antibodies, and elevated CPK. Treatment of the overlap syndrome of SLE and JPM is individualized, and the course differs between pediatric and adult patients.

Topics: Adult; Alanine Transaminase; Antibodies, Antinuclear; Arthralgia; Autoantibodies; Child; Creatine; Cyclosporins; Female; Humans; Immunoglobulin G; Lupus Erythematosus, Systemic; Methylprednisolone; Mycophenolic Acid; Myositis; Polymyositis; Rheumatoid Factor; Syndrome

Antisynthetase syndrome (AS) is a rare disease that affects patients with inflammatory myopathies such as polymyositis (PM) and dermatomyositis (DM). In patients with AS, up to 95% of patients develop antisynthetase syndrome-associated interstitial lung disease (AS-ILD). Although AS-ILD commonly occurs in patients with a well-established diagnosis of AS, it can be the first or only manifestation of an occult AS. The frequency of interstitial lung disease (ILD), myopathy, and skin involvement are often dependent on the type of myositis-specific antibodies present. AS-ILD patients who are positive for both anti-Jo-1 and anti-SSA/RO-52 autoantibodies often present with a severe degree of lung restriction on pulmonary function tests and radiologic imaging with an inadequate response toward immunosuppressive therapies. We describe a 65-year-old woman who presents with chronic dyspnea. She was initially diagnosed with corticosteroid-resistant cryptogenic organizing pneumonia based on the radiological findings on her CT chest. Her symptoms did not improve, and she suffered from intolerable corticosteroid-related side effects. Reviews of systems were positive for arthritis and Raynaud's phenomenon. She was found to have elevated inflammatory markers and autoantibodies such as anti-Jo-1, anti-RO-52, and anti-SSA. A diagnosis of AS-ILD resistant to corticosteroid therapy was made. Her lung function improved with combination therapy of mycophenolate and rituximab. Our case highlights that a detailed history and physical exam, compatible radiologic imaging, and autoantibodies are essential for the diagnosis of AS-ILD.

Topics: Aged; Antirheumatic Agents; Arthritis; Drug Therapy, Combination; Dyspnea; Female; Humans; Lung Diseases, Interstitial; Mycophenolic Acid; Myositis; Raynaud Disease; Rituximab

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Mycophenolic Acid; Myositis; Young Adult

Topics: Antibodies, Antinuclear; Autoantibodies; Humans; Lung Diseases, Interstitial; Mycophenolic Acid; Myositis; Polymyositis

Antisynthetase syndrome is a rare autoimmune disease and represents a distinct entity within the idiopathic inflammatory myopathies. Its variable systemic manifestations are composed of myositis, interstitial lung disease, non-erosive arthritis, fever, Raynaud's phenomenon, hyperkeratotic skin changes and the presence of antibodies against aminoacyl-transfer-RNA-synthetases. Interstitial lung disease is the major determinant of morbidity and mortality. The role of lung biopsy remains controversial but it might be considered on an individual basis and may provide information regarding prognosis and treatment response. An integrated clinical, radiological and pathological approach to interstitial lung disease has to be emphasised. Due to the rarity of the disease, no standardised treatment guidelines for antisynthetase syndrome exist. We discuss a patient with anti-Jo1-autoantibody antisynthetase syndrome with proximal myositis and severe, rapid onset, interstitial lung disease with a histopathological pattern of organising pneumonia on surgical lung biopsy and good response to early combined immunosuppressive treatment with corticosteroids, mycophenolate mofetil and rituximab.

Topics: Administration, Intravenous; Adrenal Cortex Hormones; Amino Acyl-tRNA Synthetases; Autoantibodies; Combined Modality Therapy; Enzyme Inhibitors; Female; Humans; Immunologic Factors; Immunosuppressive Agents; Lung; Lung Diseases, Interstitial; Middle Aged; Mycophenolic Acid; Myositis; Pneumonia; Rituximab; Severity of Illness Index; Treatment Outcome

To evaluate the efficacy and tolerability of mycophenolate mofetil (MMF) with or without calcineurin inhibitors (CNIs) in patients with inflammatory myopathy taking prednisolone, but refractory to conventional immunosuppressive therapy. The records of patients with inflammatory myopathy who had previously failed treatment with at least one immunosuppressant were retrospectively evaluated. We selected patients treated with MMF and divided them into two groups depending on whether or not there was concomitant use of CNIs. We investigated the efficacy by changes in creatine kinase (CK) levels, forced vital capacity (%FVC), prednisolone dose, and high-resolution computed tomography (HRCT) findings. Interstitial lung disease (ILD) progression was defined by more than 10% decline of %FVC from baseline. We identified 19 patients on MMF treatment. There were seven (36.8%) patients on MMF and CNIs, including five on cyclosporine and two on tacrolimus. At baseline, no significant difference was seen in the prevalence of ILD between patients taking or not taking CNIs (85.7% vs. 75.0%, P = 0.68). Improvement in CK was seen in patients treated with CNIs (P = 0.04) but not in those without (P = 0.39). No significant improvement in %FVC and HRCT findings were found in patients with ILD in either group, and there were no differences in death or ILD progression. The combination of CNIs and MMF might be more effective for decreasing CK levels than MMF alone. Neither treatment arm had a beneficial effect on ILD over a variable observation period.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Calcineurin Inhibitors; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mycophenolic Acid; Myositis; Retrospective Studies; Treatment Outcome

Topics: Adult; Dermatologic Agents; Drug Therapy, Combination; Hand Dermatoses; Humans; Male; Mycophenolic Acid; Myositis; Prednisone; Ustekinumab

The efficacy of azathioprine (AZA) and mycophenolate mofetil (MMF) for interstitial lung disease (ILD) has been described, but mainly in connective tissue disease-associated ILD. The objective of this study was to evaluate the effect of AZA and MMF on lung function and prednisone dose in myositis-related ILD (M-ILD).. In this retrospective study, patients with M-ILD seen at Johns Hopkins and treated with AZA or MMF and no other steroid-sparing agents were included. Linear mixed-effects models adjusted for sex, age, antisynthetase antibody, and smoking status were used to compare the change in FVC % predicted, diffusing capacity of the lungs for carbon monoxide (Dlco) % predicted, and prednisone dose.. Sixty-six patients with M-ILD were treated with AZA and 44 with MMF. At treatment initiation, mean FVC % predicted and Dlco % predicted were significantly lower in the AZA group than in the MMF group. In both groups, FVC % predicted improved and the prednisone dose was reduced over 2 to 5 years; however, for Dlco % predicted, only the AZA group improved. The adjusted model showed no significant difference in posttreatment FVC % predicted or Dlco % predicted between groups (mean difference of 1.9 and -8.2, respectively), but a 6.6-mg lower dose of prednisone at 36 months in the AZA group. Adverse events were more frequent with AZA than MMF (33.3% vs 13.6%; P = .04).. In M-ILD, AZA treatment was associated with improved FVC % predicted and Dlco % predicted, and lower prednisone dose. Patients treated with MMF had improved FVC % predicted and lower prednisone dose. After 36 months, patients treated with AZA received a lower prednisone dose than those treated with MMF.

Topics: Azathioprine; Enzyme Inhibitors; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Immunosuppressive Agents; Lung; Lung Diseases, Interstitial; Male; Middle Aged; Mycophenolic Acid; Myositis; Prednisone; Respiratory Function Tests; Retrospective Studies; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

Immune-mediated necrotising myopathy (IMNM) is a type of inflammatory myopathy characterised by acute or subacute severe proximal muscle weakness, significantly elevated creatine kinase levels, and prominent myofibre necrosis and regeneration with little or no inflammation. A subtype of IMNM identified by anti-HMG-CoA reductase (HMGCR)antibodies has been shown to be associated with statin exposure. Treatment of IMNM consists of immunosuppression with steroids, steroid-sparing agents, intravenous immune globulin and/or biologics. We present here a case of anti-HMCGR-associated IMNM and review the pathophysiology, diagnosis and treatment to increase physician awareness of this rare and debilitating condition.

Topics: Administration, Intravenous; Aged; Autoimmune Diseases; Biopsy; Creatine Kinase; Diagnosis, Differential; Enzyme Inhibitors; Glucocorticoids; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunoglobulins, Intravenous; Male; Methylprednisolone; Muscle Weakness; Muscular Diseases; Mycophenolic Acid; Myositis; Necrosis; Treatment Outcome

Currently, there are only few studies (mostly case reports or case series) on mycophenolate mofetil (MMF) in patients with systemic autoimmune myopathies (SAM). Therefore, the goal of the present study was to evaluate the safety and efficacy of MMF (monotherapy or coadjuvant drug) in a specific sample of patients with refractory SAM: dermatomyositis, polymyositis, anti-synthetase syndrome or clinically amyopathic dermatomyositis.. A case series including 20 consecutive adult patients with refractory SAM from 2010 to 2016 was conducted. After the introduction of MMF, associated or not with other drugs, the patients were followed for 6 consecutive months.. In 17 out of 20 patients MMF was introduced without any intolerance. The clinical symptoms evaluated in these patients were muscular, cutaneous and/or pulmonary activity. During the 6-month follow-up, 11 out of 17 patients had clinical and laboratory activities response with MMF, allowing significant tapering of the prednisone median dose (15 vs. 5 mg/day, P=0.005). On the other hand, in three out of 20 patients; MMF was discontinued in less than two months, because of gastrointestinal intolerance. There were no cases of serious infection or death.. MMF was relatively well-tolerated, safe and effective in patients with refractory SAM. Further studies are needed to confirm the data found.

Topics: Autoimmune Diseases; Dermatomyositis; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Myositis; Polymyositis; Prednisone; Retrospective Studies; Sex Factors; Statistics, Nonparametric

Topics: Forced Expiratory Volume; Humans; Immunosuppressive Agents; Lung; Lung Diseases, Interstitial; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Myositis; Prednisone; Pulmonary Diffusing Capacity; Respiratory Function Tests; Tomography, X-Ray Computed; Vital Capacity

To assess the efficacy and tolerability of mycophenolate mofetil (MMF) in six patients with myositis refractory to conventional immunosuppressive therapy.. Six patients were identified from hospital notes. All had previously failed to respond to other immunosuppressive treatments. Efficacy was measured as changes in muscle strength, creatine kinase (CK) levels and prednisolone dose.. The mean age of the group was 49.8 +/- 9.1 yrs, 6 (100%) were female and Caucasian. Patients had failed to respond to a median of 3 (range 1-3) immunosuppressive drugs. They received MMF for a mean of 22.3 +/- 18.9 months with a mean MMF dose of 1.6 +/- 0.5 g/day. The mean initial prednisolone dose was 13.7 +/- 7.7 mg and the mean follow up dose was 8.5 +/- 4.9 mg/day (P = 0.03). CK levels were reduced from mean 2395 IU/l +/- 1202.8 to 746.6 +/- 555.8 IU/l (P = 0.03).. Our data demonstrate that MMF may be effective in myositis, previously unresponsive to conventional immunosuppressive drugs.

Topics: Adult; Biomarkers; Creatine Kinase; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Middle Aged; Muscle Strength; Mycophenolic Acid; Myositis; Prednisolone; Retrospective Studies

Mycophenolate mofetil (MMF) is a new immunosuppressive agent currently being used for the prevention of renal allograft rejection. MMF is a specific inhibitor of lymphocytes and is well tolerated leading to its use in other autoimmune diseases. We have used MMF for the treatment of seven patients with inflammatory myopathy and are hereby reporting our results.. All of our patients were females (age 17-65 yr). They were symptomatic upon presentation and met classification criteria for idiopathic inflammatory myopathy. Inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein as well as creatine kinase were significantly elevated in all the patients, indicating active disease. Corticosteroids were concomitantly being administered (20-60 mg/day of prednisone). Initial therapy with conventional immunosuppressives was either ineffective or had significant adverse effects leading to their discontinuation. MMF was started in doses of 500 mg twice a day and titrated up to 1 g twice a day.. Our patients have exhibited an impressive serological response to therapy with MMF and six patients had a marked improvement in their weakness. One patient had incomplete improvement in her weakness and has required additional therapies. MMF has been well tolerated during the treatment period (12-36 months).. A striking clinical and laboratory response of active myositis in six out of seven patients in this series illustrates that MMF can be effectively used in management of autoimmune inflammatory myopathy and may be a suitable alternative to the conventional immunosuppressive agents.

Topics: Adolescent; Adult; Aged; Autoimmune Diseases; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Middle Aged; Muscle Weakness; Mycophenolic Acid; Myositis; Polymyositis; Treatment Outcome

Myositis is a rare complication following renal transplantation and is most commonly the result of drug-mediated myotoxicity. Other causative disorders include viral infection, electrolyte imbalance and myositis of autoimmune origin. We describe a 60-year-old patient who developed acute polymyositis 4 weeks after a 000 human leukocyte antigen (HLA) mismatch cadaveric renal transplant. Following an uncomplicated transplant course with maintenance triple immunosuppression (prednisolone, mycophenolate mofetil and cyclosporine), the patient presented with severe symmetrical proximal muscle weakness associated with a rise in serum creatine kinase to 46800 U/L. Electromyography confirmed myopathic changes and muscle biopsy demonstrated extensive muscle-fiber necrosis with an inflammatory infiltrate. There were no obviously culpable drugs and viral studies were negative. Prompt initiation of high-dose steroid therapy led to clinical and biochemical recovery. Acute polymyositis may occur following renal transplantation. Potential mechanisms include viral antigen transmission or a localized form of graft vs. host disease.

Topics: Acute Disease; Anti-Inflammatory Agents; Antigens; Creatine Kinase; Cyclosporine; Electrolytes; Electromyography; HLA Antigens; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Inflammation; Kidney Transplantation; Male; Middle Aged; Muscles; Mycophenolic Acid; Myositis; Polymyositis; Prednisolone; Time Factors

The authors report the use mycophenolate mofetil (MM) in the treatment of neuromuscular diseases. Thirty-eight patients (32 with MG, three with inflammatory myopathy, and three with chronic acquired demyelinating neuropathy) were treated with MM for an average duration of 12 months. All patients tolerated MM without major side effects. Twenty-four patients improved either in their functional status or in their ability to reduce corticosteroid dose. Mean time to improvement was 5 months.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Myositis; Retrospective Studies; Treatment Outcome